Stage 3, lecture 5, 2014-2015
Immunity
Immunity composed of two types
1. Innate immunity. *
2. Adaptive immunity. **
Protection against infection that relies on mechanisms that
exist before infection, and react essentially in the same way
to repeated infections in innate reaction, but much
stronger in the adaptive response immunity.
There are generally two kinds of immunity:
A. Active immunity.
B. Passive immunity.
Active immunity is conferred by a host response to a
microbe or microbial antigen, whereas passive immunity is
conferred by adaptive transfer of antibodies or T
lymphocytes specific for the microbe.
Both forms of immunity provide resistance to infection
(immunity) and are specific for microbial antigens, but only
active immune responses generate immunologic memory.
Innate Immunity*
The innate immunity is called natural immunity or native
immunity.
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There are two different mechanisms of defense in the
innate immunity.
A. Cellular defense mechanism.
B. Biochemical defense mechanism.
These mechanisms react only to noninfectious substances
and they respond essentially in the same way to repeated
infections.
Important: The native immunity present or exist before infection.
The principal components of innate immunity are:
1. Physical and chemical barriers such as
a. Skin.
b. Epithelia.
c. Antimicrobial substances produced from the
surfaces of the epithelial.
2. Phagocytic cells (neutrophils, macrophages), natural
killer (NK) cells.
3. Blood proteins including: a. members of complement
system. b. Mediators of inflammation.
Mechanisms of innate immunity
Physiologic barriers at the portal of entry the skin
A. Skin
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1. Skin mostly prevents pathogens to penetrate it, some
high virulent microorganisms are capable of penetrating
intact skin and cause diseases.
2. Skin resistance may vary with age like in children, their
skin is highly susceptible to ringworm infection. After
puberty, the resistance to fungi increases due to increased
content of saturated fatty acids in sebaceous secretions.
B. Mucus membrane
1. Respiratory tract:
a. The film of mucus covers the tissue surface and is
constantly being driven upward by ciliated cells to the
natural orifices.
b. Mucus and tears contain lysozyme and other
antimicrobial substances mucus, and when bacteria stick to
the mucus become eliminated by the lethal effect of
lysozyme.
c. Binding or attachment of bacteria to the receptors present
on epithelial surfaces (by means of bacterial adhesins) is
the first step in the colonization and infection.
d. The epithelial cells have IgA antibodies on the surface,
may eliminate the attachment of bacteria.
e. Microorganisms that enter the body via mucus
membrane may be taken by phagocytes then be transported
to the lymph nodes.
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2. Gastrointestinal tract:
a. Saliva contains a number of hydrolytic enzymes able to
kill bacteria.
b. The low pH of the stomach kills many ingested bacteria
especially Vibrio cholera.
c. Small intestine contains many proteolytic enzymes and
active macrophages.
d. Normal microbial flora the mucus membranes interferes
with the other pathogenic bacteria and fungi limiting their
dominance.
C. Complement activation:
a. The alternative complement pathway can be activated by
microbial surfaces as a very important and first line defense
against infections. Alternative pathway can be carried out
in the absence of Abs.
b. Mechanism by which complement contributes to host
defense including some steps like opsonization, lysis of
microbes and amplification of inflammatory responses.
D. Phagocytes:
a. Phagocyte cells (granulocytes, macrophages) are
circulating and increase during bacterial infections.
b. The main functions of phagocytic cells are: 1. Migration,
2.Chemotaxis, 3. Ingestion and 4.Microbial killing.
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c. Many microorganisms elaborate chemotactic factors that
attract phagocytes.
E. Cytokines:
a. Cytokines are proteins produced by many different cell
types that mediate inflammatory and immune reactions.
a. Cytokines are small soluble protein molecules having
variety of properties, produced by one cell and influence
the other cells.
b. Cytokines are proteins released by lymph cells which act
as a cellular mediator and control immune response
(mediators of communication between cells of the immune
system).
d. Cytokines are molecularly characterized and are assigned
as interleukin (IL) with number like IL-1, IL-2 etc.
Cytokines that mediate and regulate innate immunity:
1. Tumor Necrosis Factor (TNF) is the principal mediator
of the acute inflammatory response to gram-negative
bacteria and other infectious microbes and is responsible
for many systemic complications of severe infections.
2. Interleukin-1 is the principal function of IL-1, similar to
stimuli.
3. Chemokines are a large family of structurally
homologous cytokines that stimulate leukocyte movement
and regulate the migration of leukocytes from the blood to
tissues.
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F. Interferon:
a. The term interferon drives from the ability to interfere
with viral infection. Viral infection produces expression of
antiviral proteins, inhibit viral replication and known as
interferons.
b. Two distinct groups of proteins called interferon-alpha
(INF-α) and interferon-beta (INF-β), both interferons called
interferon type I and is distinct from interferon-gamma
(INF-γ), type II.
c. Type II produced by activated T lymphocytes. Alpha and
beta interferons help control viral replication by inhibiting
protein synthesis in cells.
G. Natural Killer (NK) Cells:
1. NK cells are a distinct functional population of
lymphocytes.
2. They play important role in antibody-dependent cellular
cytotoxicity (ADCC) having role in the early phases of
infection with herpes viruses and other intracellular
pathogens.
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3. They look like granular lymphocytes morphologically
related to T cells.
4. They do not express antigen-specific receptors.
5. They have two types of surface receptors, including an
"activating receptor" that recognizes carbohydrate ligands
and an "inhibitory receptor" that recognizes MHC class I
molecules.
6. They can lyse target cells that have undergone malignant
transformation playing role in immune surveillance against
tumor establishment.
7. They can kill certain virus-infected cells with altered
levels of MHC class I molecules.
8. The lytic activity of NK cells is enhanced by high levels
of alpha-interferon and beta-interferon.
Adaptive immunity **
The form of immunity that is mediated by lymphocytes and
stimulated by exposure to infectious agents. This immunity
is characterized with specificity and memory, the ability to
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respond more strongly to repeated exposure to the same
microbe.
There are two important cell types playing a crucial role in
the adaptive immunity:
A. B lymphocytes (called also B cells) responsible to
produce antibodies.
B. T lymphocytes responsible to produce the effector
cells.
Adaptive immunity composed of:
1. Humoral immunity:
a. Humoral immunity, which is mediated by molecules
in the blood and mucosal secretions called antibodies,
that are produced by B cells.
b. Humoral immune responses is initiated by binding
of antigens to membrane-bound molecules, thus
initiate the recognition process.
2. Cell-mediated immunity (cellular immunity).
a. Defense against intracellular microbes, viruses and
toxins.
b. To kill the infected cells in order to remove the
reservoirs of the infections.
c. Phagocytosed microbes by the macrophage.
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Antibodies
The basic structural unit of an antibody is composed of:
a. Two identical heavy polypeptide chains.
b. Two light polypeptide chains.
They are linked together by disulfide bonds.
*Antibody complexed with antigen activates complement
through ‫״‬classical pathway‫״‬
*The acute inflammatory reactions can also be initiated by
antibody bound to mast cell.
* Antibodies can block interactions between:
a. A virus and a cell.
b. Nutrient and bacterium.
c. A toxin and its cellular receptor.
Definitions
**(Macrophage is a tissue-based phagocytic cell derived from
blood monocytes that plays important roles in innate and
adaptive immune responses. Macrophages are activated by
microbial products such as endotoxin and by T cell cytokines like
IFN-gamma.
Activated macrophages phagocytose and kill
microorganisms, secrete proinflammatory cytokines and present
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antigens to helper T cell).
**(Antibodies (Abs) are a sorted of glycoprotein molecules
produced by B lymphocytes and are also called
immunoglobulin(Ig). They are produced by B lymphocytes that
bind antigens (Ags) ,often with high degree of specificity and
affinity.
** Neutrophil (polymorphonuclear leukocyte, PMN)
A phagocytic cell characterized by segmented lobular nucleus
and cytoplasmic granules filled with degratative enzymes. PMNs
are circulating white blood cells and the major cell type
mediating acute inflammation responses to bacterial infections.
**Mast cell is the major effector cell immediate hypersensitivity
(allergic) reactions, it is derived from marrow, reside in most
tissues adjacent to blood vessels, express high-affinity Fc
receptor for IgE.
**Antigen: a molecule that binds to an antibody or T cell
receptor (TCR). Antigens that bind to antibodies include all
classes of molecules. TCRs bind only peptide fragments of
protein complex.
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**Type I interferon,(INF-α and INF-β):Type I interferon consist
of two distinct groups of proteins. INF-α is actually a family of
about 20 structually related polypeptides and a single INF-β.
** Type II interferon, Interferon-γ (IFN-γ): a cytokine produced
by T lymphocytes and NK cells whose principal function is to
activate macrophages in both innate immune responses and
adaptive cell-mediated immune responses. The major source of
INF-α is mononuclear phagocytes, whereas INF-β produced by
many cells.
** Natural killer (NK) cells: they are a subset of bone marrow
derived lymphocytes, distinct from B and T cells, that function in
innate immune responses to kill microbe-infected cells by direct
lytic mechanisms and by secreting INF-γ. NK cells do not express
clonally distributed antigen receptors like Ig receptors or TGRs.
Their activation is regulated by a combination of cell surface
stimulatory and inhibitory receptors, the later recognizing self
MHC molecules
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